HIV-1 is primarily transmitted via the mucosal route. Therefore we have used a nonhuman primate model of mucosal SHIV infection to assess the efficacy of various anti-HIV-1 bnAbs. We have shown that the anti-HIV-1 bnAbs VRC01 and 10E8 that target the CD4 binding site(CD4bs) and the Membrane proximal region (MPER)on the HIV-1 envelope glycoprotein, respectively, can effectively protect nonhuman primates against mucosal SHIV challenge when administered at very low doses to these animals before mucosal challenge with a pathogenic SHIV1. Furthermore, we have demonstrated that adding a Fc mutation that increases binding to the neonatal Fc receptor improves the serum half life and mucosal retention of VRC01 in nonhuman primates2. This mutation also leads to increased protective efficacy against a mucosal challenge with SHIV. In addition, through a combination of next-generation sequencing, computational bioinformatics, and structure-guided design, we have developed a more potent version of VRC01, VRC07-523-LS3. VRC07-523-LS exhibits about a 5-8 fold increase in in vitro neutralization potency compared to VRC01, and it provided protection to nonhuman primates at 5-fold lower concentrations than VRC01 against a mucosal challenge with SHIV.